Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming.

ABSTRACT: Cancers commonly reprogram translation and metabolism, but little is known about how these two features coordinate in cancer stem cells. Here we show that glioblastoma stem cells (GSCs) display elevated protein translation. To dissect underlying mechanisms, we performed a CRISPR screen and identified YRDC as the top essential transfer RNA (tRNA) modification enzyme in GSCs. YRDC catalyzes the formation of N⁶-threonylcarbamoyladenosine (t⁶A) on ANN-decoding tRNA species (A denotes adenosine, and N denotes any nucleotide). Targeting YRDC reduced t⁶A formation, suppressed global translation and inhibited tumor growth both in vitro and in vivo. Threonine is an essential substrate of YRDC. Threonine accumulated in GSCs, which facilitated t⁶A formation

SUBMITTER: Wu X 

PROVIDER: S-EPMC11552442 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature